| Autor: |
Lyamzaev, Konstantin, Pustovidko, Antonina, Simonyan, Ruben, Rokitskaya, Tatyana, Domnina, Lidia, Ivanova, Olga, Severina, Inna, Sumbatyan, Natalia, Korshunova, Galina, Tashlitsky, Vadim, Roginsky, Vitaly, Antonenko, Yuriy, Skulachev, Maxim, Chernyak, Boris, Skulachev, Vladimir |
| Předmět: |
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| Zdroj: |
Pharmaceutical Research; Nov2011, Vol. 28 Issue 11, p2883-2895, 13p |
| Abstrakt: |
Purpose: To develop effective mitochondria-targeted antioxidants composed entirely of natural constituents. Methods: Novel mitochondria-targeted antioxidants were synthesized containing plant electron carrier and antioxidant plastoquinone conjugated by nonyloxycarbonylmethyl residue with berberine or palmatine, penetrating cations of plant origin. These compounds, SkQBerb and SkQPalm, were tested in model planar phospholipid membranes and micelles, liposomes, isolated mitochondria and living cells. Results: SkQBerb and SkQPalm penetrated across planar bilayer phospholipid membrane in their cationic forms and accumulated in mitochondria isolated or in living human cells in culture. Reduced forms of SkQBerb and SkQPalm as well as C10Berb and C10Palm (SkQBerb and SkQPalm analogs lacking plastoquinol moiety) revealed radical scavenging activity in lipid micelles and liposomes, while oxidized forms were inactive. In isolated mitochondria and in living cells, berberine and palmatine moieties were not reduced, so antioxidant activity of C10Berb and C10Palm was not detected. SkQBerb and SkQPalm inhibited lipid peroxidation in isolated mitochondria at nanomolar concentrations; their prooxidant effect was observed at 1,000 times higher concentrations. In human cell cuture, nanomolar SkQBerb and SkQPalm prevented fragmentation of mitochondria and apoptosis induced by exogenous hydrogen peroxide. Conclusion: This is the first successful attempt to construct mitochondria-targeted antioxidants composed entirely of natural components, namely plastoquinone, nonyl, acetyl and berberine or palmatine residues. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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